`The stress of dying': the role of heat shock proteins in the regulation of apoptosis

Heat shock proteins (Hsps) are a family of highly homologous chaperone proteins that are induced in response to environmental, physical and chemical stresses and that limit the consequences of damage and facilitate cellular recovery. The underlying ability of Hsps to maintain cell survival correlates with an inhibition of caspase activation and apoptosis that can, but does not always, depend upon their chaperoning activities. Several mechanisms proposed to account for these observations impact on both the "intrinsic", mitochondria-dependent and the "extrinsic", death-receptor-mediated pathways to apoptosis. Hsps can inhibit the activity of pro-apoptotic Bcl-2 proteins to prevent permeabilization of the outer…